Processing and characterization of glass-ceramic foams belonging to the Li2O-ZrO2-Al2O3-SiO2 (LZSA) system produced by gelcasting

In this work the viscosimetry technique was used to evaluate the rheological characteristics of ceramic suspensions prepared with a LZSA (Li2O-ZrO2-SiO2-Al2O3) glass. From the rheological characterization it was possible to establish optimized conditions of solid fraction, dispersant, organic monomers and foaming agent for the production of glass-ceramic foams by gelcasting. The resulting foams were subjected to heattreatments at 200-500ºC/60 min, for degradation of organics and at 950ºC/60 min for sintering and crystallization. With the obtained porous ceramic bodies linear thermal shrinkage, apparent density and mechanical strength measurements as well as microstructural analysis were performed. The adaptation of the rheological characteristics of the LZSA parent glass powder with the gelcasting processing technique allowed the production of ceramic foams with high open and interconnected porosity (>90%) with good thermal stability and with mechanical strength suitable for the production of porous ceramics.Neste trabalho, a técnica de viscosimetria foi utilizada para avaliar as características reológicas de suspensões preparadas com precursor vitrocerâmico do sistema LZSA (Li2O-ZrO2-SiO2-Al2O3). A partir da caracterização reológica, foi possível estabelecer condições composicionais adequadas de fração de sólidos, dispersante e monômeros orgânicos. A quantidade de agente espumante para produção de espumas vitrocerâmicas por gelcasting foi determinada pela variação volumétrica após agitação. As espumas resultantes foram submetidas a tratamentos térmicos no intervalo de temperatura compreendido entre 200 e 500ºC/60 min, para degradação da matéria orgânica e a 950ºC/60 min para sinterização e cristalização. Com os corpos cerâmicos porosos foram realizadas medidas de retração térmica, densidade aparente, análise microestrutural e resistência mecânica. A adequação das características reológicas do precursor LZSA por gelcasting permitiu a produção de espumas com elevada porosidade (> 90%) aberta e interconectada com boa estabilidade térmica e com resistência mecânica compatível com cerâmicas [email protected]@[email protected]@emc.ufsc.brUniversidade Federal de Santa Catarina Departamento de Engenharia Mecânica Programa de Pós-Graduação em Ciência e Engenharia de MateriaisCentro Universitário Barriga Verde - UNIBAVEUniversidade Federal de São Paulo (UNIFESP) Departamento de Ciência e TecnologiaUNIFESP, Depto. de Ciência e TecnologiaSciEL

The relationship between target joints and direct resource use in severe haemophilia

Objectives Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related direct costs (NDDCs) has not been studied. Methods Data on haemophilia patients without inhibitors was drawn from the ‘Cost of Haemophilia across Europe – a Socioeconomic Survey’ (CHESS) study, a cost assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the United Kingdom) in which 139 haemophilia specialists provided demographic and clinical information for 1285 adult patients. NDDCs were calculated using publicly available cost data, including 12-month ambulatory and secondary care activity: haematologist and other specialist consultant consultations, medical tests and examinations, bleed-related hospital admissions, and payments to professional care providers. A generalized linear model was developed to investigate the relationship between NDDCs and target joints (areas of chronic synovitis), adjusted for patient covariates. Results Five hundred and thirteen patients (42% of the sample) had no diagnosed target joints; a total of 1376 target joints (range 1–10) were recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average mean effect EUR 779; p < 0.001). Conclusions Our analysis suggests that the presence of one or more target joints has a significant impact on NDDCs for patients with severe haemophilia, ceteris paribus. Prevention and management of target joints should be an important consideration of managing haemophilia patients

Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells

The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro

DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Despite the significant progress made in colon cancer chemotherapy, advanced disease remains largely incurable and novel efficacious chemotherapies are urgently needed. Histone deacetylase inhibitors (HDACi) represent a novel class of agents which have demonstrated promising preclinical activity and are undergoing clinical evaluation in colon cancer. The goal of this study was to identify genes in colon cancer cells that are differentially regulated by two clinically advanced hydroxamic acid HDACi, vorinostat and LBH589 to provide rationale for novel drug combination partners and identify a core set of HDACi-regulated genes.</p> <p>Methods</p> <p>HCT116 and HT29 colon cancer cells were treated with LBH589 or vorinostat and growth inhibition, acetylation status and apoptosis were analyzed in response to treatment using MTS, Western blotting and flow cytometric analyses. In addition, gene expression was analyzed using the Illumina Human-6 V2 BeadChip array and Ingenuity^®Pathway Analysis.</p> <p>Results</p> <p>Treatment with either vorinostat or LBH589 rapidly induced histone acetylation, cell cycle arrest and inhibited the growth of both HCT116 and HT29 cells. Bioinformatic analysis of the microarray profiling revealed significant similarity in the genes altered in expression following treatment with the two HDACi tested within each cell line. However, analysis of genes that were altered in expression in the HCT116 and HT29 cells revealed cell-line-specific responses to HDACi treatment. In addition a core cassette of 11 genes modulated by both vorinostat and LBH589 were identified in both colon cancer cell lines analyzed.</p> <p>Conclusion</p> <p>This study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets that are modulated by HDACi, providing much-needed information on HDACi mechanism of action and providing rationale for novel drug combination partners. We identified a core signature of 11 genes which were modulated by both vorinostat and LBH589 in a similar manner in both cell lines. These core genes will assist in the development and validation of a common gene set which may represent a molecular signature of HDAC inhibition in colon cancer.</p

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer's Disease (AD) and cerebral ischemia. Specifically epsilon, delta, and gamma PKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of epsilon PKC, such as psi epsilon Receptor for Activated C-Kinase (psi epsilon RACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing epsilon PKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of delta PKC and gamma PKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration